In vivo, the tumor microenvironment is a complex milieu containing multiple cell types including tumor cells, vascular cells such as endothelial cells, and stromal cells, such as fibroblasts. In addition, in vivo, these cells are exposed to blood flow and various biological transport conditions. In vivo, microvascular cells in a tumor are affected by blood flow and communicate with tumor and non-tumor cells, both physically and through diffusible factors. In addition, the tumor vasculature is abnormal, characterized by chaotic branching, a low flow rate, and leaky vessels, and thus serves as a major transport barrier to anticancer therapies that target tumor cells. The interplay between tumor cells, endothelial cells, and stromal cells affects each cell type, leading to increased angiogenesis and tumor cell proliferation, and this crosstalk may be an important factor in determining the responsiveness of tumor cells to anticancer drugs.
Conventional in vitro tumor models using static monocultures of tumor cells fail to adequately model in vivo tumor biology. Current in vitro tumor models also do not accurately predict efficacy and safety of anticancer therapies in vivo. Traditional in vitro studies performed under static conditions are generally poor predictors of drug sensitivity, due to the lack of representation of components of the tumor microenvironment. Furthermore, the conventional models often do not exhibit responses to drugs or compounds at concentrations that produce the response in vivo, instead requiring much higher concentrations of the drug or compound to induce the same response. Thus, there exists a need in the art for methods for accurately mimicking the in vivo tumor microenvironment in vitro. Such methods would improve the accuracy of preclinical screening of anticancer agents for efficacy and safety.